Involvement of the p53 and p73 transcription factors in neuroAIDS.

Cell Cycle
Ruma MukerjeeBassel E Sawaya

Abstract

HIV-associated dementia (HAD) is the most common AIDS-associated neurological disorder and is characterized by the development of synaptodendritic injury to neurons. To advance HAD therapy, it is crucial to identify the mechanisms and factors involved. The viral protein HIV-1 Tat is among those factors and is released by HIV-1-infected cells and can be taken up by adjacent neuronal cells leading to neurotoxic effects. Multiple cellular host proteins have been identified as Tat cofactors in causing neuronal injury. Interestingly, most of these factors function through activation of the p53 pathway. We have now examined the ability of Tat to activate the p53 pathway leading to the induction of endogenous p53 and p73 in neuronal cells. We found that Tat induced p53 and p73 levels in SH-SY5Y cells and that this induction caused retraction of neurites. In the absence of either p53 or p73, Tat failed to induce dendritic retraction or to activate the proapoptotic proteins, such as Bax. Further, we found that p53-accumulation in Tat-treated cells depends on the presence of p73. Therefore, we conclude that Tat contributes to neuronal degeneration through activation of a pathway involving p53 and p73. This information will be valuable fo...Continue Reading

Citations

Feb 3, 2011·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Kathryn E Medders, Marcus Kaul
Oct 1, 2011·The Journal of Biological Chemistry·J Robert ChangBassel E Sawaya
Nov 2, 2011·Neuro-degenerative Diseases·J Robert ChangBassel E Sawaya
Dec 24, 2013·Virology Journal·Asen Bagashev, Bassel E Sawaya
May 30, 2014·Apoptosis : an International Journal on Programmed Cell Death·Asen BagashevBassel E Sawaya
Apr 2, 2016·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Francesca Isabella De SimoneKamel Khalili
Sep 26, 2014·The Journal of General Virology·Soo Jin Kim, Paul K Y Wong
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Dec 29, 2012·Aging·Francesca Grespi, Gerry Melino
Dec 29, 2018·The Journal of Biological Chemistry·Maryline SanterreBassel E Sawaya
May 7, 2009·Current Opinion in Neurology

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